Abstract
A goal for scientists studying septic acute kidney injury (AKI) should be to formulate a conceptual model of disease that is able to coherently reconcile the molecular and inflammatory consequences of sepsis with impaired epithelial tubular function, diminished glomerular filtration rate (GFR) and ultimately kidney failure. Recent evidence has shed light on how sepsis modulates the tubular regulation of ion, glucose, urea and water transport and acid-base homeostasis in the kidney. The present review summarizes recent discoveries on changes in epithelial transport under septic and endotoxemic conditions as well as the mechanisms that link inflammation with impaired tubular membrane transport. This paper also proposes that the tubular dysfunction that is mediated by inflammation in sepsis ultimately leads to increased sodium and chloride delivery to the distal tubule and macula densa, contributing to tubuloglomerular feedback and impaired GFR. We feel that this conceptual model resolves many of the physiologic and clinical paradoxes that septic AKI presents to practicing researchers and clinicians.